Encapsulation of particulate solids and of liquid droplets is commonly done for purposes of controlled release, environmental protection or rendering inert reactive, toxic or hazardous materials. Coating of pharmaceuticals, pesticides, catalysts and discrete electronic elements are some specific examples of applications involving microencapsulation techniques.
There are many different reasons to coat active pharmaceutical agents. First if the active substance is coated it can mask the taste of unpleasant tasting substances. In other cases, the medicament is encapsulated in forms called enteric formulations to prevent the active substance from being exposed to stomach acids. Erythromycin base is readily destroyed in the presence of stomach acid. Attempts to enterically coat erythromycin base is a common subject of the pharmaceutical literature. Enteric formulations are designed to allow the drug to pass through the acidic environment of the stomach without disintegration and yet disintegrate in the duodeneum. Aspirin is often formulated in enteric forms to prevent it from irritating the lining of the stomach. Commonly used coatings for enteric substances are those of the phthalate family especially cellulose acetate phthalate.
Other reasons that drugs are often encapsulated or formulated in delayed release or sustained release form is to prolong the active lifetime of drugs with a short half life. A drug such as nitrofuradantoin is quickly absorbed by the gut and is quickly eliminated by the kidney. However, it is desirable that the nitrofuradantoin be at a high constant plasma level. Microencapsulation can avoid the requirement that a patient take it more times during the day and thus the problems with patient compliance.
In other instances, the drugs are formulated in delayed release form to lessen toxic effects. If it is released all at once in the gut excessively high levels of drugs may be reached. Whereas if the drug is a sustained release form, a therapeutic level but not a toxic level may be achieved. The literature has many examples of formulations of theophylline to allow a therapeutic dose without toxic symptoms.
There are several different types of microencapsulation techniques employed for encapsulation and microencapsulation of pharmaceuticals.
One such method is pan coating. This is an older method developed in the 1880's. This method is used to coat pharmaceutical tablets as well as candies and the like. The disadvantage with this is that it requires rather large particles on the order of several millimeters to several centimeters in size.
Another method is the Wurster coating method. The Wurster coating is an extremely powerful and versatile method for microencapsulation that was developed by Dale Wurster at the University of Wisconsin in the 1960's. It is often called fluid bed coating. The smallest size that the Wurster coater can use is about 100 microns and more realistically about 150 microns. This requires a solid core and utilizes a fluidized bed of air. This means that any material sensitive to oxygen or moisture would be very difficult to process.
A third method of microencapsulation is spray drying. Spray drying is an older method of microencapsulation than the Wurster coating method. Its actual usage is primarily more in the area of foods such as solid drink mixes. Spray drying requires an excessively large amount of capsule wall on the order of 80% on a volume basis. Spray drying is done at elevated temperatures to remove moisture which means that there is a possibility of degrading temperature sensitive pharmaceuticals.
In employing any of these methods coating uniformity is a constant concern. In the case of the pan coating and Wurster coating the capsule walls are applied as droplets on the order of 40 microns in size and above. The droplet size is more likely to be 100-200 microns. The uniformity of the coating then relies upon the uniformity of depositing these relatively large droplets of wall material. This causes some non-uniformity in the coating when these droplets are large compared to the core material. In the case of spray drying the wall is actually a matrix and the small droplets of core material are embedded in it much as a peanut cluster. Some droplets are close to the surface of the particle and some are very deep within. Further, a wall applied as a liquid must flow on wet. This presents problems around sharp surfaces of the core material. Thus in all of these processes coating uniformity varies substantially.
One form of microencapsulation which has not been utilized for pharmaceuticals is vapor deposition of polymeric films. This technology relates both to the vacuum vapor deposition of polymers such as poly-p-xylylene (Parylene) and also to glow discharge polymerized films such as polyolefins including ethylene and methylene, styrene, chlorotrifluoroethylene, tetrafluoroethylene, tetramethyldisuloxane and the like. These methods are generally disclosed in the "Biocompatability of Glow Discharge Polymerized Films and Vacuum Deposited Parylene" in the Journal of Applied Polymer Science: Applied Polymer Symposium 38, 55-64 (1984).
Vapor deposited Parylene is used to coat many different substrates including particulate substrates. The method of coating particulate material with Parylene is disclosed for example in Gorham et al U.S. Pat. No. 3,300,332. Primarily the Parylene is used in applications where absolute protection of the coated substrate is required. Examples of these would be coating of reactive metals such as lithium and sodium, coating of catalysts to prevent reaction and coating of electronic components to prevent environmental degradation of the component. In biological applications the Parylene coatings are used to protect implanted materials and prevent rejection of the materials by the body's defenses. Exemplary applications are disclosed for example in Synthetic Biomedical Polymers Concepts and Applications Copyright 1980 Technomic Publishing Co. pp 117-131. Coating of integrated circuits to be implanted in the body is disclosed in Blood Compatability of Components and Materials in Silicone Integrated Circuits, Electronic Letters Aug. 6, 1981, 17 (16). The use of Parylene generally in orthopedic uses is also discussed in Parylene Biomedical Data a 1975 publication of the Union Carbide Co. Parylene because of its strength, biological compatability and general inertness in physiological environments has made it generally suitable as an orthopedic coating for implant devices and the like. This same durability would suggest that it is unsuitable for pharmaceutical application.